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Biomedical subjects

P Liberini

Publications and source records attributed to P Liberini.

At least 19 recordsLinked to original sources
PubMed1996

Increase of aldosterone secretion following acute haloperidol administration: possible clinical implications.

The present study was designed to investigate the effect of haloperidol on plasma corticosteroid levels in a small sample of unmediated psychiatric patients requiring acute care. Seven young male normotensive subjects in metabolic balance received a single dose of haloperidol (2 mg i.v.). Blood samples were collected for the radioimmunoassay of plasma renin activity, cortisol and aldosterone concentration at baseline and 3, 6, 12 and 24 h after injection. In five out of seven patients a significant, transient elevation of plasma aldosterone level was observed within 12 h from administration. In contrast, plasma renin activity and cortisol concentration were unchanged. Possible clinical implications of the neuroleptic-associated aldosterone elevations are discussed.

Adult↗
PubMed1996

Expression of nerve growth factor in brown adipose tissue: implications for thermogenesis and obesity.

The presence of nerve growth factor (NGF) and the ability of adrenergic stimulation to affect the rate of its synthesis in mouse, rat, and human brown adipose tissue (BAT) were investigated. Addition of conditioned medium, obtained from preconfluent and confluent brown adipocytes, to PC12 cells induced typical morphological changes similar to those due to NGF itself. Anti-NGF antibodies blocked this action. Moreover, NGF mRNA was detected by RT-PCR both in BAT and in brown adipocyte preparations. That NGF is synthesized in and released from brown fat cells was confirmed by immunoblotting. When the animals were exposed to low temperatures, NGF production declined. The effect of cold exposure could be mimicked by the addition of norepinephrine (NE) at day 4 or 8 (preconfluent and confluent cells, respectively). NE depletion obtained by reserpine injection induced a drastic increase of BAT NGF production. In both rat and human BAT, immunohistochemistry identified distinct anatomical structures that express the low affinity neurotropin receptor, termed p75NGFR. BAT production of NGF was higher in genetically obese rats and mice than in their lean counterparts, a difference that becomes more evident with age. Prolonged exposure to low temperature significantly decreased the BAT NGF synthesis also in obese animals. We conclude that NGF is synthesized in and released from brown fat cells, its production being inversely dependent on sympathetic activity, in both physiological and pathophysiological conditions, and increased in genetic animal models of obesity.

Adipose Tissue, Brown↗
PubMed1995

NGF-mediated synaptic sprouting in the cerebral cortex of lesioned primate brain.

In the present study, coronal brain sections of cortically devascularized non-human primates (Cercopithecus aethiops) were used to assess the lesion-associated synaptic loss, and the effect of exogenous nerve growth factor (NGF) in preventing or reversing this neurodegeneration. The sections were immunolabeled with antibodies against the synaptic marker protein synaptophysin (SYN), as well as choline acetyltransferase (ChAT) and parvalbumin (PV) markers that identify cholinergic neurons and interneurons, respectively. We found that, compared to sham-operated animals, in the lesioned vehicle treated animals SYN immunoreactivity near the lesioned site in the frontoparietal cortex was decreased by 31%. Similarly, corrected optical density values of immunostained sections specific for ChAT in the nucleus basalis of Meynert (ipsilateral to the lesion) decreased by 20% and PV-immunoreactive neurons near the lesion decreased by 47%. In contrast, NGF-treated lesioned animals showed levels of SYN, ChAT, and PV immunoreactivity similar to sham controls. These results are consistent with previous studies and support the view that NGF may not only prevent neurodegenerative changes after neocortical infarction by protecting vulnerable neurons, but also is capable of inducing sprouting and synaptogenesis.

Animals↗
PubMed1995

Nerve growth factor treatment restores [3H]QNB binding site density in adult rat subjected to cortical infarction.

The effects of unilateral cortical devascularization and nerve growth factor treatment on muscarinic cholinoceptors labelled with [3H]QNB were investigated in rat cerebral cortex. The lesion induced a significant ipsilateral decrease in the density (Bmax) but not in the affinity (kD) of [3H]QNB binding sites. Intraventricular infusion of 2.5 S mouse nerve growth factor (NGF) increased the density of binding sites such that Bmax values of lesioned animals treated with NGF were not different from control subjects.

Animals↗
PubMed1995

Alz-50 recognizes epitopes in primary sensory fibres and in neurons of the substantia gelatinosa of the spinal cord. An ultrastructural study in the rat.

The monoclonal antibody Alz-50 has been proposed as a marker for cellular pathological changes in Alzheimer's disease. However, it has been reported that this antibody also reacts with specific epitopes in normal individuals. Furthermore, intense Alz-50 immunoreactivity has been recently described in the hypothalamus and spinal cord of rat and monkey. In the present study, we analysed the distribution pattern of Alz-50 immunostaining in the spinal cord of the adult rat. Using light microscopy, immunostained fibres and varicosities were detected mainly in laminae I-II, although some immunostaining lamina I and the outer two thirds of lamina II. The varicosities appeared either scalloped or dome-shaped and contained numerous agranular synaptic vesicles and a few dense-core vesicles. Most varicosities were presynaptic to dendrites. A few immunostained cell bodies and dendrites were also observed, but glial cells were never immunostained. Some ultrathin sections were processed for postembedding immunogold detection of calcitonin gene-related peptide and GABA immunoreactivities. Most of the varicosities which were immunoreactive for Alz-50 also showed calcitonin gene-related peptide immunoreactivity. In contrast, GABA immunoreactivity was never co-localized with Alz-50 immunoreactivity. These results indicate that, in the superficial dorsal horn, the epitope recognized by the Alz-50 antibody is located mainly, but not exclusively, in primary sensory fibres.

Animals↗
PubMed1995

Tau protein immunolocalization in fetal and adult human spinal cord.

In the present study, the monoclonal antibody Alz-50 has been used to determine and compare the immunohistochemical localization of phosphorylated tau proteins in the developing and normal adult spinal cord. At all stages of fetal life Alz-50 fiber immunoreactivity was observed in the dorsal roots, in the dorsal and dorsolateral funiculi, and in restricted regions of the dorsal horn. Alz-50 immunoreactivity was also demonstrated in the dorsal root ganglion neurons. In the adult spinal cord a consistent pattern of Alz-50 fiber immunoreactivity was localized in the superficial layers of the dorsal horn (lamina I and II) but not in dorsal and dorsolateral funiculi and in the dorsal root ganglion. Comparable results in fetal specimens have been obtained employing PHF-1, a monoclonal antibody generated against paired helical filament proteins from Alzheimer brains, while no significant immunostaining for PHF-1 was observed in the adult spinal cord. In addition, the staining with monoclonal and polyclonal anti-tau antibodies overlapped with that of Alz-50. The transient, selective pattern of Alz-50 and PHF-1 immunoreactivity may disclose some relevant functions of tau proteins during somatosensory pathway development.

Adult↗
PubMed1994

Neocortical infarction in subhuman primates leads to restricted morphological damage of the cholinergic neurons in the nucleus basalis of Meynert.

The aim of the present study was to investigate the long-term effect of cortical infarction on the subhuman primate (Cercopithecus aethiops) basal forebrain. The lesion, carried out by cauterizing the pial blood vessels supplying the left fronto-parieto-temporal neocortex, induced retrograde degenerative processes within the ipsilateral nucleus basalis of Meynert. The morphometrical analysis revealed that significant shrinkage of cholinergic neurons and loss of neuritic processes were localized within the intermediate regions of the nucleus basalis. The average cross-sectional areas of choline acetyltransferase-immunoreactive neurons in the intermedio-ventral (Ch4iv) and intermedio-dorsal (Ch4id) nucleus basalis were decreased to 62.5 +/- 9.5 and 58.0 +/- 8.6%, respectively, of the sham-operated values. Although an apparent loss of Nissl-stained magnocellular neurons in Ch4iv and Ch4id was found by applying a quantitative analysis based on a perikaryal-size criterion, data obtained by the quantification of immunostained material failed to reveal any significant decrease of cholinergic cell density. Results are discussed in view of future application of this ischemic model to study processes of retrograde degeneration following cortical target removal and to assess potential neurotrophic and neuroprotective properties of pharmacologic agents.

Animals↗
PubMed1994

Encapsulated genetically engineered fibroblasts: release of nerve growth factor and effects in vivo on recovery of cholinergic markers after devascularizing cortical lesions.

Genetically engineered rat fibroblasts producing nerve growth factor (NGF) were encapsulated in alginate-polylysine-alginate gels with the objective to produce viable "minifactories" continuously producing and secreting NGF into the rat brain. Microencapsulated fibroblasts (NGF secretors and NGF non-secretors) were placed onto the surface of the lesioned rat cortex (unilateral devascularizing lesion) and animals were sacrificed 30 days after surgery. Fibroblasts NGF-non secreters normally produce tumors after implantation, therefore, they were irradiated prior to encapsulation. Three other experimental groups were studied in parallel: non-lesioned (controls), lesioned rats receiving "empty" alginate spheres and lesioned animals without treatment and microspheres. Biochemical analysis of microdissected brain tissues of lesioned animals treated with encapsulated NGF-secretor fibroblasts showed a significant increase in choline acetyltransferase (ChAT) activity in cortices adjacent to the lesion but not far from it (entorhinal cortex). This may indicate a gradient of concentration of the released NGF and/or differential responsivity of lesioned vs non-lesioned target tissue. ChAT enzymatic activity in the microdissected nucleus basalis magnocellularis (NBM) was significantly decreased (P < 0.05) in all lesioned animals treated with spheres without fibroblasts and those with fibroblasts not secreting NGF. Morphometric analysis of ChAT-IR and low affinity NGF-receptor IR cholinergic neurons in the middle portion of the NBM shows a prevention of neuronal shrinkage and extensive neuropil in animals treated with microencapsulated NGF-secretor fibroblasts. The results of this study demonstrate that NGF from encapsulated genetically engineered fibroblasts can be secreted for at least long enough to prevent degenerative changes of cholinergic neurons in the NBM.

Alginates↗
PubMed1993

Alz-50 immunoreactivity in the central nervous system of adult rat and primate.

The purpose of this work was to investigate the distribution and density of Alz-50 immunoreactivity in the central nervous system of normal adult and cortically injured rats and primates (Cercopithecus aethiops). In control animals of both species a consistent pattern of fiber immunoreactivity was detected within the hypothalamus (arcuate nucleus and median eminence) and the spinal cord (posterior horn and dorsal root nerve). Immunoreactive perikarya were predominantly observed throughout the anterior region of the third ventricle. An identical localization and density of Alz-50 staining was observed in lesioned animals. These experiments reveal that the pattern of Alz-50 immunoreactivity is not affected by the neurodegenerative processes that follow the cortical devascularizing lesion. These observations suggest that the monoclonal antibody Alz-50, besides recognizing cytoskeletal components in degenerating neurons, reacts with specific epitopes located in the hypothalamus and spinal cord of normal mammalian central nervous system.

Animals↗
PubMed1993

Long-term protective effects of human recombinant nerve growth factor and monosialoganglioside GM1 treatment on primate nucleus basalis cholinergic neurons after neocortical infarction.

Neocortical infarction induces biochemical and morphological retrograde degenerative changes in cholinergic neurons of the rat nucleus basalis magnocellularis [Sofroniew et al. (1983) Brain Res. 289, 370-374]. In the present study, this lesion model has been reproduced in the non-human primate (Cercopithecus aethiops) to investigate whether degenerative changes affecting the cortex surrounding the lesioned area and the ipsilateral basal forebrain are prevented by the early administration of recombinant human nerve growth factor alone or in combination with the monosialoganglioside GM1. Six months after surgery and treatment, the monkeys were processed either for biochemistry (choline acetyltransferase assay) or immunocytochemistry. In lesioned vehicle-treated animals, choline acetyltransferase activity significantly decreased by 28% in the cortex surrounding the injured area and by 31% in the ipsilateral nucleus basalis of Meynert when compared with values of sham-operated monkeys. These biochemical changes were fully prevented with the administration of nerve growth factor alone or in combination with the monosialoganglioside GM1. The morphometrical analysis revealed a significant shrinkage of cholinergic neurons (61 +/- 1.4% of sham-operated cell size) and loss of neuritic processes (59 +/- 10% of sham-operated values) within the intermediate nucleus basalis region of lesioned vehicle-treated animals. Although a protection of the cholinergic cell bodies within the nucleus basalis was found with both treatments, a significant recovery of the neuritic processes (84 +/- 7.2% of sham-operated values) was assessed only in the double-treated monkeys. These results indicate that the early administration of nerve growth factor alone or in combination with the monosialoganglioside GM1 induces a long-term protective effect on the nucleus basalis cholinergic neurons in cortical injured non-human primates.

Animals↗